We propose to conduct a prospective study to test the hypothesis that women with low selenium intake are at increased risk of developing cancer. Work in vitro and animal studies demonstrate that selenium supplements reduce the incidence of carcinogeninduced and spontaneous neoplasms. The human evidence is scanty, but areas with high levels of selenium in the soil or blood seem to have lower rates of cancer, and cancer patients generally tend to have lower levels of selenium. The study will be conducted among the 121,964 married, registered nurses, ages 36-61, who are participants in the Nurses' Health Study, an ongoing cohort study of the determinants of cancer and cardiovascular disease. In 1982 we will request that each participant mail back a sample of toenail clippings. Based on pilot surveys, we anticipate that about 64,000 will comply. Keratinous structures concentrate seleium and other trace elements, and their analysis can provide a good estimate of long-term exposure. A pilot study has indicated that nail specimens are preferable to hair because the latter may be seriously contaminated by selenium-containing shampoos, and because a sufficient mass of nail tissue can more easily be obtained. We propose to analyze the specimens by instrumental neutron activation which is an accurate, highly sensitive, non-destructive technique. The samples collected in 1982 will be stored until the 1984 follow-up questionnaires are returned. At that point, nail samples from women who subsequently developed cancer will be analyzed for selenium, along with randomly selected control samples from women who did not develop cancer. Because of the large number of participants, we anticipate a sufficient number of incident cancers to provide about 95% power to detect a relative risk (RR) of 1.8 (at the .05 alpha level) between upper and lower quintiles of selenium. On the basis of prior work, breast and colon cancer are sites most likely to be associated with selenium. For these cancers, there will be about 90% power to detect RRs of 2.1 and 2.8 respectively.